Ex Parte Marr et alDownload PDFPatent Trial and Appeal BoardDec 21, 201613581016 (P.T.A.B. Dec. 21, 2016) Copy Citation United States Patent and Trademark Office UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O.Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 13/581,016 08/24/2012 Amy Louise Marr X19034 7810 25885 7590 12/23/2016 FT T T TT T Y fr TOMPANY EXAMINER PATENT DIVISION IVANOVA, SVETLANA M P.O. BOX 6288 INDIANAPOLIS, IN 46206-6288 ART UNIT PAPER NUMBER 1627 NOTIFICATION DATE DELIVERY MODE 12/23/2016 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): patents @ lilly.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte AMY LOUISE MARR, JANE GRANVILLE OWENS, DOUGLAS EUGENE MOUZIN, and KARI LYNETTE RIGGS1 Appeal 2015-003257 Application 13/581,016 Technology Center 1600 Before DONALD E. ADAMS, MELANIE L. McCOLLUM, and RYAN H. FLAX, Administrative Patent Judges. McCOLLUM, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35U.S.C. § 134 involving claims to a method of controlling or treating pain. The Examiner has rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. STATEMENT OF THE CASE Claims 1, 2, 4, 5, 8—14, 25, 29, 32, and 33 are pending and on appeal (App. Br. 1—2). Claim 1 is representative and reads as follows: 1. A method of controlling pain comprising transdermally administering to an equine in need thereof a therapeutically effective amount 1 Appellants identify the real party in interest as Eli Lilly and Company (App. Br. 2). Appeal 2015-003257 Application 13/581,016 of a composition comprising fentanyl, a penetration enhancer, and a volatile liquid, wherein the composition is a solution. Claims 1, 2, 4, 5, 8—14, 25, 29, 32, and 33 stand rejected under 35 U.S.C. § 103(a) as obvious over Klose2 in view of Orsini3 and Wegner4 (Ans. 4). The Examiner relies on Klose for disclosing “a transdermal drug delivery system which comprises: a therapeutically effective amount of an analgesic; at least one dermal penetration enhancer,. . . and at least one volatile liquid” and “a method for administering at least one systemic acting analgesic to an animal which comprises applying an effective amount of the analgesic in the form of the drug delivery system of the present invention” {id. at 4—5). The Examiner finds that Klose’s “Examples 1, 2, 4 and 5 specifically disclose compositions of fentanyl, octyl salicylate and aqueous ethanol” {id. at 5). The Examiner also finds that the “analgesic may be in a solution or suspension” {id.). In addition, the Examiner finds that “[diseases or conditions that may be treated by using the drug delivery system and methods of Klose include, but are not limited to chronic pain conditions, post-operative pain, and neuropathic pain” {id.). The Examiner also finds that, “[p]er Klose, the invention extends to both humans and non- 2 Klose et al., US 2004/0028625 Al, Feb. 12, 2004. 3 J. A. Orsini et al., Pharmacokinetics of Fentanyl Delivered Transdermally in Healthy Adult Horses — Variability Among Horses and its Clinical Implications, 29 J. Vet. Pharmacol. Therap. 539-546 (2006). 4 Kirsten Wegner et al., How to Use Fentanyl Transdermal Patches for Analgesia in Horses, 48 AAEP Proceedings 291—294 (2002). 2 Appeal 2015-003257 Application 13/581,016 human animals (which a person of skill in the art would understand to include horses)” (id.). The Examiner relies on Orsini for disclosing “a study aimed at determining the pharmacokinetics of fentanyl delivered transdermally in adult horses” and “that for a transdermal dosage of 60-67 pg/kg (which falls within Appellants’] claimed dose range), there were no adverse effect attributable to fentanyl in any of the horses, indicating that this dosage is safe in systematically healthy adult horses” (id. at 6). The Examiner acknowledges that Orsini discloses “that this dosage . . . failed to achieve plasma fentanyl concentration generally considered to be analgesic (> ng/ml) in about one-third of the horses” (id.). The Examiner relies on Wegner for disclosing “a study of how to use fentanyl transdermal patches for analgesia in horses” and “that clinical cases of fentanyl patches as part of pain management include for laminitis and colitis, and various other visceral sources of pain, specifically colic pain” (id.). The Examiner concludes: [I]t would have been obvious to a person of skill in the art at the time of the invention to combine the teachings of Klose, Orsini and Wegner to arrive at Appellants’] claimed dosage with a reasonable expectation of success. A person of skill in the art would have been motivated to do so in view of the disclosure in Orsini, which points to dosages of fentanyl on transdermal delivery, which have already been determined as safe, as well as guided by the knowledge in the art of the needed plasma fentanyl concentration considered to be analgesic. As the art discloses, the assays for determining such plasma concentrations and effective doses were already in place, and with studies already conducted on them in horses. Thus, it would have been obvious 3 Appeal 2015-003257 Application 13/581,016 to a person of skill in the art at the time of the invention to optimize the specific dosage for the specific composition of Klose with a reasonable chance of success. (Id. at 6—7.) FINDINGS OF FACT 1. Klose discloses “a transdermal drug delivery system which comprises: a therapeutically effective amount of an analgesic; at least one dermal penetration enhancer . . . ; and at least one volatile liquid” (Klose, Abstract). 2. Klose also discloses “a method for administering at least one systemic acting analgesic to an animal which comprises applying an effective amount of the analgesic in the form of the drug delivery system of the present invention” (id.). 3. In addition, Klose discloses that “[ajnalgesics that may be used in the drug delivery system of the present invention include . . . fentanyl” (id. 126). 4. Klose also discloses that “[pjreferably the animal is a human but the invention also extends to the treatment of non-human animals” (id. 131). 5. In addition, Klose discloses that a “co-solvent or other standard adjuvant, such as a surfactant, may be required to maintain the analgesic in solution or suspension at the desired concentration” (id. 137). 6. Klose also discloses: A particular advantage of the drug delivery system of the present invention is that patient compliance is improved as the system does not occlude the skin. As a result local irritation and allergic sensitization problems arising from prolonged exposure of the 4 Appeal 2015-003257 Application 13/581,016 skin to both the delivery system of occlusive transdermal patch devices and the adhesive used to affix these patches to the skin are reduced. (Id. 143.) 7. In addition, Klose discloses that “[diseases or conditions that may be treated by using the drug delivery system and methods of the present invention include, but are not limited to chronic pain conditions, post operative pain, restless leg syndrome, opioid dependence and neuropathic pain” (id. 1 58). 8. Orsini discloses that the “safety and pharmacokinetics of fentanyl, delivered transdermally at a dosage of 60—67 pg/kg, were investigated in six healthy adult horses” (Orsini, Abstract). 9. In particular, Orsini discloses: Three transdermal fentanyl patches (Duragesic®), each containing 10 mg of fentanyl citrate, were applied to the mid dorsal thorax of each horse and left in place for 72 h. Plasma fentanyl concentrations were periodically measured throughout this period and for 12 h after patch removal. After an initial delay of approximately 2 h, the plasma fentanyl concentration rose rapidly in a fairly linear fashion, reaching a peak at around 12 h; thereafter, it gradually declined in a roughly linear manner over the next 72 h. (Id.) 10. In addition, Orsini discloses: “No adverse effects attributable to fentanyl were observed in any of the horses, indicating that this dosage is safe in systemically healthy adult horses. However, it failed to achieve plasma fentanyl concentrations generally considered to be analgesic (>1 ng/mL) in about one-third of horses.” (Id.) 5 Appeal 2015-003257 Application 13/581,016 11. Wegner discloses: The inclusion of fentanyl patches as part of pain management in equine clinical cases at the University of Florida Large Animal Teaching Hospital has been limited to date. However, the consistent and often significant improvement in clinical signs of visceral pain in these patients when fentanyl patches were employed supports their continued use___Transdermal fentanyl uptake in horses is rapid, likely because of sebaceous gland as well as transdermal passage, with plasma levels over 2 ng/ml within 4 h of patch application. Plasma levels peak at 6—9 h after patch application and remain above 1 ng/ml for up to 54 h after application, but fall rapidly when the patch is removed. When patches were reapplied in 48-to 72-h intervals, average steady- state levels of 1.9 and 1.2 ng/ml, respectively, were obtained.. . . We were surprised that cases with distinct visceral pain, such as colitis or pleuritis, seemed notably more comfortable, even when doses below 10 mg/150 kg were used. (Wegner 293 (footnotes omitted).) ANALYSIS Klose discloses “a transdermal drug delivery system which comprises: a therapeutically effective amount of an analgesic[, such as fentanyl]; at least one dermal penetration enhancer . . . ; and at least one volatile liquid” (Finding of Facts (FF) 1 & 3). Klose also discloses “a method for administering at least one systemic acting analgesic to an animal[, including a non-human animal,] which comprises applying an effective amount of the analgesic in the form of the drug delivery system of the present invention” (FF 2 & 4). Orsini and Wegner each disclose the transdermal delivery of fentanyl to an equine (FF 8 & 11). We agree with the Examiner that it would have been prima facie obvious to administer Klose’s system to an equine (Ans. 6—7). 6 Appeal 2015-003257 Application 13/581,016 Appellants argue, however, that “Klose is not properly combinable with Orsini and Wegner” (App. Br. 6). In particular, Appellants argue that “Klose continually teaches that its invention ‘relates to a system for the non occlusive delivery to an animal of analgesics[,]’” whereas “Orsini and Wegner only teach the use of transdermal fentanyl patches for analgesia in horses, which is clearly a system for the occlusive delivery of analgesics to horses” (id.). Appellants also argue that the “non-occlusive drug delivery system taught by Klose would lead a person of ordinary skill in the art away from Orsini and Wegner, which both teach an occlusive drug delivery system” (id.). In addition, Appellants argue that “one of skill in the art would conclude that incorporating the features of Orsini and Wegner into Klose . . . would destroy the intent or purpose of the invention disclosed in Klose” (id. at 6—7). We are not persuaded. The Examiner is not bodily incorporating the teachings of Orsini and Wegner into Klose. Instead, the Examiner is relying on Orsini and Wegner to suggest transdermally administering Klose’s composition to an equine, in particular, and to suggest doses that may be therapeutically effective (Ans. 5—6). Therefore, we do not agree with Appellants that the Examiner’s combination would destroy the intent or purpose of Klose’s invention, nor do we agree with Appellants that Klose teaches away from the combination. Appellants also argue that “the Examiner has failed to provide a clear articulation of the reasons why the claimed methods would have been obvious over Klose in view of Orsini and further in view of Wegner” (App. Br. 7). In particular, Appellants argue that “Klose provides no teaching or suggestion as to what dosage is needed for administration to an equine for 7 Appeal 2015-003257 Application 13/581,016 controlling pain” (id. at 8). In addition, Appellants argue that, “although the study in Orsini does not demonstrate any adverse effects, it does not prove (i) that the dosage used in Orsini is safe and (ii) whether dosage can result in adverse effects attributable to fentanyl” (id. ). Appellants also argue that “[njeither Orsini nor Wegner provide any guidance regarding the dosage needed for administration to an equine for controlling pain because these references use only natch formulations” and “one of ordinary skill in the art would not equate transdermal administration of a patch formulation with transdermal administration of a solution” (id. at 9). We are not persuaded. Klose discloses “a transdermal drug delivery system which comprises: a therapeutically effective amount of an analgesic” (FF 1). We recognize that Klose does not teach what doses would be required for equine. However, both Orsini and Wegner provide guidance as to suitable amounts (FF 8 & 11). In particular, Orsini discloses the transdermal delivery of fentanyl at a dosage of 60-67 pg/kg (= 0.06-0.067 mg/kg) (FF 8) and Wegner discloses “doses below 10 mg/150 kg” (= doses below 0.067 mg/kg) (FF 11), which are within the scope of the present claims (see dependent claim 29, which recites “a dose of about 0.01 to about 0.1 mg/kg of weight of the equine” (App. Br. 15)). In addition, Appellants have not provided evidence that the amounts suggested by the prior art would not have provided guidance to one of ordinary skill in the art regarding amounts that could be used for administering Klose’s composition to equine. Given these disclosures, we agree with the Examiner that “it would have been obvious to a person of skill in the art at the time of the invention to optimize the 8 Appeal 2015-003257 Application 13/581,016 specific dosage for the specific composition of Klose with a reasonable chance of success” (Ans. 7). In addition, Appellants argue that the “instant rejection is improperly based on impermissible hindsight” (App. Br. 11). However, as discussed above, we conclude that the Examiner has provided reasoning, based on the prior art, as to why the references would have been combined (Ans. 5—6). Appellants also argue that the claimed invention yields unexpected properties (App. Br. 11). We are not persuaded. The Specification does state that the “maximum mean plasma concentration of fentanyl observed in equines was at least four times greater than the targeted therapeutic concentration {i.e., about 1 ng/ml) observed in canines and in humans” (Spec. 34). The Specification also states: Pharmacokinetic parameters of fentanyl in equines administered the composition of the present invention are unique compared to pharmacokinetic parameters in canines administered the composition of the present invention. For example, the amount of fentanyl absorbed into the systemic circulation of equines following transdermal administration of the composition is unexpectedly higher than anticipated based on comparative allometric calculations of fentanyl absorption in canines. Furthermore, significantly higher doses of transdermally administered fentanyl are necessary to obtain a fentanyl plasma concentration of at least 1 ng/ml in canines. {Id. at 34—35 (emphasis added).) However, we do not agree that this evidence is sufficient to overcome the strong prima facie case of obviousness. In support of these statements, the Specification refers to Table 1 {id.). We note that Table 1 discloses a faster time to obtain (and a shorter duration of) a plasma concentration of > 1 ng/ml for equine as compared to canine 9 Appeal 2015-003257 Application 13/581,016 (id. at 35). However, Wegner recognizes that “[tjransdermal fentanyl uptake in horses is rapid, likely because of sebaceous gland as well as transdermal passage” (FF 11), thus suggesting that the faster time was likely not unexpected. In addition, the Specification, citing to prior art, states that “[vjarious studies of fentanyl administration via a transdermal patch formulation indicate that the therapeutically effective dose of fentanyl is lower in equines compared to canines” (Spec. 35). Thus, it is not clear to us how the data supports the conclusion “that the amount of fentanyl absorbed into the systemic circulation of equines following transdermal administration of the composition is unexpectedly higher than anticipated based on comparative allometric calculations of fentanyl absorption in canines” (id. ). We also note that claim 1 is not commensurate with this evidence given that it encompasses a range that “may vary from one equine to another and can depend upon a number of factors, including the overall physical condition of the equine and the underlying cause of the condition to be treated” and, thus, may include those amounts that may be required for canines and/or humans (see id. at 11). CONCLUSION The evidence supports the Examiner’s conclusion that Klose, Orsini, and Wegner suggest the method of claim 1. We therefore affirm the obviousness rejection of claim 1. Claims 2, 4, 5, 8—14, 25, 29, 32, and 33 have not been argued separately and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv). 10 Appeal 2015-003257 Application 13/581,016 TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED 11 Copy with citationCopy as parenthetical citation